We plan to study carcinogenesis by N-nitroso compounds related to (1) environmental carcinogenesis, (2) compounds inducing common human tumors, such as of the colon-rectum, pancreas and esophagus, and (3) mechanisms of action, especially with respect to DNA alkylation. Thus we shall evaluate nitrosamine and nitrosourea formation from precursors including NO2), in rodents, by determining these compounds in vivo and by measuring alkylation of gastric wall DNA. The influence of ascorbate, polyhydric phenols, etc. on in vivo nitrosation will be tested. We shall examine the effect of possible environmental promoters on esophageal carcinogensis by a nitrosamine; effects of N-nitroso compounds on acute toxic responses in the liver, including DNA sedimentation; the effect of modifying the chemical structure of bis(betahydroxyalkyl) nitrosamines on carcinogenesis in the colon and pancreas; use of antigenic methods for detecting the development of pancreatic tumors; and transplacental carcinogenesis by bis(betahydroxyalkyl) nitrosamines, and the effect thereon of promoting agents. In mechanistic studies, we shall examine why two nitrosoureas are powerful liver carcinogens in rats; whether nucleic acid alkylation by three cyclic nitrosamines is correlated with differences in organ specificity; and in biochemical and biologic studies, why diallylnitrosamine is carcinogenic for the hamster but not the rat.